Di-17alpha(delta4-androsten-17beta-ol-3-one) butadiyne



rates 3,051,733 DI-17a(A -ANDRsTEN-17.B-0L-3-0NE) BUTADIYNE John A.Zderic, Palo Alto, Calif., and Pierre Crabbe,

Mexico City, Mexico, assignors, by mesne assignments, to SyntexCorporation, a corporation of Panama No Drawing. Filed Oct. 3, 1961,Ser. No. 142,482 5 Claims. (Cl. 260-3974 In the above formula Rrepresents hydrogen or methyl; R represents hydrogen or a hydrocarboncarboxylic acyl group of less than 12-carbon atoms.

The acyl group is derived from hydrocarbon carboxylic acids containingless than 12 carbon atoms which may be saturated or unsaturated, ofstraight, branched, cyclic or cyclic-aliphatic chain, aromatic and maybe substituted by functional groups such as hydroxy, alkoxy containingup to 5 carbon atoms, acyloxy containing up to 12 carbon atoms, nitro,amino or halogen. Typical ester groups are the acetate, propionate,enanthate, benzoate, trimethylacetate, t-butylacetate, phenoxyacetate,cyclopentylpropionate, aminoacetate and fl-c'hloropropionate.

The novel compounds of the present invention are prepared by the processillustrated by the following equation:

In practicing the process just outlined the l7u-ethynyl- $351,733Patented Aug. 28, 1962 testosterone or the 19-nor derivative thereof (I)is treated with cupric acetate in a suitable solvent such as pyridine,at approximately 50 C. for a period of time of the order of 3 hours thusfurnishing the corresponding di-l7a(A androsten-l7fl-ol-3-one) butadiynederivative (II;R =H). This derivative is conventionally acylated with anexcess of an acylating agent as for example acetic anhydride or caproicanhydride, affording the corresponding l7fi-acyloxy compound (II; R=acy1oxy).

The following specific examples serve to illustrate but are not intendedto limit the scope of the present invention.

Example I T o 500 ml. of pyridine containing 5 g. ofl7a-ethynyltestosterone, there were added g. of cupric acetate. Theresulting mixture was kept at 50 C. for 3 hours with constant stirring.After cooling the mixture was filtered and the precipitate washed withbenzene. The combined filtrates were evaporated almost to dryness undervacuum. After dilution with benzene, the solution was washed with water,dilute acid and water, then dried over sodium sulfate, treated withactive charcoal, filtered and the filtrate concentrated to a smallvolume, whereupon there crystallized di-17a(A -androsten-17B-ol-3-one)butadiyne.

Following the same procedure there was treated 17wethynyl-l9-nor-testosterone, affording dl17a(19-11OI'Aandr0sten-17B-ol-3-0ne) butadiyne.

Example II Using the same conditions described in Example II, butsubstituting acetic anhydride by propionic anhydride, there were treateddi-17a-(A -androsten-l7/8-o1-3-one) butadiyne and di-17u(l9-nor-A-androsten-l7fi-ol-3-one) butadiyne furnishing respectively di-17a(A-androsten- 17fl-ol-3-one-l7-propionate) butadiyne and di17a(l9- nor-A-androsten-1713-01-3-one-17-propionate) butadiyne.

Example IV Following the technique described in Example II, butsubstituting acetic anhydride by caproic anhydride andcyclopentylpropionic anhydride, there were correspondingly obtained thecaproates and cyclopentylpropionates of the starting compounds ofExample III.

We claim:

1. A compound of the following formula:

f P 3,051,733 H V i P 3 i V v 4 wherein R is a member of the groupconsisting of hy- 4. Di-17a(A -androsten-17 8-o1-3-one-17-acetate)butadrogen and methyl and R is selected from the group diyne. consistingof hydrogen and a hydrocarbon carboxylic 5. Di-17a(19-nor Aandrosten-17/8-o1-3-one-17-aceacid of less than 12 carbon atoms. tate)butadiyne.

2. Di-17a(A -androsten-17fl-o1-3-one) butadiyne. 5 3. 'Di-17a(19-nor Aandrosten-l7fi-o1-3-one) buta- W 7 N r f r n e cit d,

diyne.

1. A COMPOUND OF THE FOLLOWING FORMULA: